Exogenous porcine surfactants increase the infiltration of leukocytes in the lung of rats.

BACKGROUND: Several studies have investigated the influence of exogenous surfactants on inflammatory response in the lung, however results reported about effects of surfactants on the lung infiltration of leukocytes are controversial. Our previous study noticed that treatment of porcine surfactant (PS) significantly increased the lung infiltration of leukocytes in rats with acute lung injury (ALI). The objective of this study was to verify the effect of exogenous PS on the lung infiltration of leukocytes in vivo and investigate the possible mechanisms involved in vitro. METHODS: The number of leukocytes in bronchoalveolar lavage fluid (BALF) of rats with or without lipopolysaccharide (LPS)-induced ALI was determined after treatment with different concentrations of PS, dexamethasone (Dex) or PS + Dex. The effect of PS and Curosurf, a commercially available porcine surfactant, on human peripheral neutrophil migration was determined by the Boyden Chamber Assay. RESULTS: Instillation of PS significantly increased the number of leukocytes in BALF of normal rats and rats with LPS-induced ALI. Most of the increased leukocytes were neutrophils. Dex significantly decreased the number of leukocytes and TNF-alpha concentration in BALF caused by LPS, but did not significantly reduce the number of leukocytes increased by PS. In vitro experiments further demonstrated that both PS and Curosurf had direct chemotactic effects on neutrophils. CONCLUSIONS: These results suggest that PS contain chemoattractant(s) which induce the infiltration of leukocytes, especially neutrophils, into lung.

Aerosolised surfactant generated by a novel noninvasive apparatus reduced acute lung injury in rats.

INTRODUCTION: Exogenous surfactant has been explored as a potential therapy for acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). In the present study, a nebuliser driven by oxygen lines found in the hospital was developed to deliver aerosolised porcine pulmonary surfactant (PPS). We hypothesised that aerosolised surfactant inhaled through spontaneous breathing may effectively reduce severe lung injury. METHODS: Rats were intravenously injected with oleic acid (OA) to induce ALI and 30 minutes later they were divided into five groups: model (injury only), PPS aerosol (PPS-aer), saline aerosol (saline-aer), PPS instillation (PPS-inst), and saline instillation (Saline-Inst). Blood gases, lung histology, and protein and TNF-alpha concentrations in the bronchoalveolar lavage fluid (BALF) were examined. RESULTS: The PPS aerosol particles were less than 2.0 mum in size as determined by a laser aerosol particle counter. Treatment of animals with a PPS aerosol significantly increased the phospholipid content in the BALF, improved lung function, reduced pulmonary oedema, decreased total protein and TNF-alpha concentrations in BALF, ameliorated lung injury and improved animal survival. These therapeutic effects are similar to those seen in the PPS-inst group. CONCLUSIONS: This new method of PPS aerosolisation combines the therapeutic effects of a surfactant with partial oxygen inhalation under spontaneous breathing. It is an effective, simple and safe method of administering an exogenous surfactant.

[Influence of porcine pulmonary surfactant administered at different time on therapeutic effects in rats with oleic acid induced acute lung injury].

OBJECTIVE: To investigate the therapeutic effects of endotracheal instillation porcine pulmonary surfactant (PPS) given at different time on acute lung injury (ALI) induced by oleic acid (OA). METHODS: Arterial blood gases and respiratory rate during the experiments, survival rate, lung index, total protein (TP) contents in bronchoalveolar lavage fluid (BALF), tumor necrosis factor-alpha (TNF-alpha) level in plasma, light microscopy of the lung at 4 hours after the experiments were examined in different groups of Sprague-Dawley (SD) rats: Group 1, sham group; Group 2, injected intravenously with OA 0.2 ml/kg; Group 3, injected intravenously with OA 0.2 ml/kg+PPS 100 mg/kg 0.5 hour after OA; Group 4, injected intravenously with OA 0.2 ml/kg+PPS 150 mg/kg 0.5 hour after OA; Group 5, injected intravenously with OA 0.2 ml/kg+PPS 100 mg/kg 2 hours after OA; Group 6, injected intravenously with OA 0.2 ml/kg+PPS 150 mg/kg 2 hours after OA. RESULTS: Giving PPS not only improved the rats' (Group 3, Group 4 and Group 6) arterial blood gases and reduced respiratory rate, but also significantly raised their 4 hours-survival rate and decreased lung index, protein contents in BALF and TNF-alpha level in plasma, ameliorated pathohistological changes compared with Group 2 and Group 5 (all P<0.05). CONCLUSION: PPS (100 mg/kg) administered at the early stage (0.5 hour after OA) provides obvious effects on respiratory efficiency and alleviates lung injury in rats with OA induced ALI, PPS (150 mg/kg) at the late stage (2 hours after OA) has the same effects mentioned above, however PPS (100 mg/kg) given 2 hours after ALI has no therapeutic effects.

[Influence of different doses of porcine pulmonary on the therapeutic effects in rats with oleic acid induced acute lung injury].

OBJECTIVE: To investigate the therapeutic effects and dose effect relationship of intratracheal instillation of different doses of porcine pulmonary surfactant (PPS) in rats with oleic acid (OA) induced acute lung injury (ALI). METHODS: Arterial blood gases and respiratory rate during the experiments, survival rate, lung index, total protein (TP) content in bronchoalveolar lavage fluid (BALF), tumor necrosis factor-alpha (TNF-alpha) level in plasma, light microscopy examination of lung specimens after the experiments were determined and performed in control group, OA (0.2 ml/kg) + saline, OA + PPS 50 mg/kg, OA+PPS 80 mg/kg, OA+PPS 100 mg/kg, OA+PPS 150 mg/kg, OA+PPS 200 mg/kg groups, respectively. RESULTS: In PPS 50 mg/kg group, arterial blood gases were improved and respiratory rate was reduced during the first 2 hours (P<0.05). Arterial blood gases and reduced breath rates respiratory rate were not improved in other PPS treatment groups but 4 hours-survival rate was lowered, lung index was decreased, protein content s in BALF and TNF-alpha level in serum were lowered, and pathological changes were ameliorated compared with group given saline after OA, especially in high dosage of PPS (150-200 mg/kg) group (P<0.05). CONCLUSION: Administration of PPS via trachea provides obvious effects on respiratory functions in rats with OA induced ALI, moreover PPS (> or =80 mg/kg) alleviates lung injury. There is no dose-effect relationship of PPS in PPS-treatment groups.